Biologic and immunomodulatory properties of mesenchymal stromal cells derived from human pancreatic islets

• Published in: Cytotherapy (Oxford, England) Vol. 14; no. 8; pp. 925 - 935
• Main Authors: Kim, Jaehyup, Breunig, Melissa J, Escalante, Leah E, Bhatia, Neehar, Denu, Ryan A, Dollar, Bridget A, Stein, Andrew P, Hanson, Summer E, Naderi, Nadia, Radek, James, Haughy, Dermot, Bloom, Debra D, Assadi-Porter, Fariba M, Hematti, Peiman
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01-09-2012; Informa Healthcare
• Subjects: Advanced Basic Science; Antigens, Surface - analysis; Bone Marrow Cells - cytology; Bone Marrow Cells - immunology; Bone Marrow Cells - metabolism; Cadaver; Cell Differentiation; Cell Proliferation; Cells, Cultured; Flow Cytometry; Gene Expression; Humans; immunomodulation; Islets of Langerhans - cytology; Islets of Langerhans - immunology; Islets of Langerhans - metabolism; mesenchymal stromal cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - immunology; Mesenchymal Stromal Cells - metabolism; Other; pancreatic islet transplantation; pancreatic islets; immunomodulation; pancreatic islets; mesenchymal stromal cells; pancreatic islet transplantation
• ISSN: 1465-3249; 1477-2566
• DOI: 10.3109/14653249.2012.684376

Abstract Background aims Mesenchymal stromal cells (MSC) have now been shown to reside in numerous tissues throughout the body, including the pancreas. Ex vivo culture-expanded MSC derived from many tissues display important interactions with different types of immune cells in vitro and potentially play a significant role in tissue homeostasis in vivo . In this study, we investigated the biologic and immunomodulatory properties of human pancreatic islet-derived MSC. Methods We culture-expanded MSC from cadaveric human pancreatic islets and characterized them using flow cytometry, differentiation assays and nuclear magnetic resonance-based metabolomics. We also investigated the immunologic properties of pancreatic islet-derived MSC compared with bone marrow (BM) MSC. Results Pancreatic islet and BM-derived MSC expressed the same cell-surface markers by flow cytometry, and both could differentiate into bone, fat and cartilage. Metabolomics analysis of MSC from BM and pancreatic islets also showed a similar set of metabolic markers but quantitative polymerase chain reactions showed that pancreatic islet MSC expressed more interleukin(IL)-1b, IL-6, STAT3 and FGF9 compared with BM MSC, and less IL-10. However, similar to BM MSC, pancreatic islet MSC were able to suppress proliferation of allogeneic T lymphocytes stimulated with anti-CD3 and anti-CD28 antibodies. Conclusions Our in vitro analysis shows pancreatic islet-derived MSC have phenotypic, biologic and immunomodulatory characteristics similar, but not identical, to BM-derived MSC. We propose that pancreatic islet-derived MSC could potentially play an important role in improving the outcome of pancreatic islet transplantation by promoting engraftment and creating a favorable immune environment for long-term survival of islet allografts.